Dysfunctional blood monocytes may predict CVD risk in patients with type 2 diabetes: Study

The findings imply that assessing monocyte count and frequency is a valuable predictive marker for the risk of CV events in diabetes patients.

Previous studies have shown diabetes to be a major risk factor for atherosclerotic cardiovascular diseases (ASCVD) with a 2-fold higher risk of CV events in patients with diabetes compared with those without. However, there is cardiovascular risk heterogeneity among patients with T2D that cardiovascular risk scores fail to detect. None of these cardiovascular risk scores considers proatherogenic immune effector, monocyte blood count.

Circulating monocytes are inflammatory effector cells involved in type 2 diabetes and atherogenesis. Nicolas Venteclef, IMMEDIAB Laboratory, Paris, France, and colleagues investigated the relationship between circulating monocytes and CV risk progression in people with T2D, using phenotypic, metabolomic, and transcriptomic analyses in a cross-sectional study population of 672 participants with T2D.

The study led to the following findings:

· Coronary artery calcium score was positively correlated with blood monocyte count and frequency of the classical monocyte subtype.

· Unsupervised k-means clustering based on monocyte subtype profiles revealed 3 main endotypes of people with type 2 diabetes at varying risk of cardiovascular events. These observations were confirmed in a validation cohort of 279 T2D participants.

· The predictive association between monocyte count and major adverse cardiovascular events was validated through an independent prospective cohort of 757 patients with T2D.

· Integration of monocyte transcriptome analyses and plasma metabolomes showed a disruption of mitochondrial pathways (tricarboxylic acid cycle, oxidative phosphorylation pathway) that underlined a proatherogenic phenotype.

The findings reveal an association between routine white blood cell-derived monocyte counts and CV risk among patients with T2D. By combining monocyte immunophenotypic, immunophenotypic, and plasma metabolomic analyses, the researchers showed an oxidative phosphorylation and mitochondrial modulation in a specific monocyte subtype, linked to an endotype of type 2 diabetes patients that are at higher cardiovascular risk.

We show an association of 2 phenomena: an increase in the monocyte pool, resulting in more ready infiltration of atherosclerotic plaques promoting progression," the researchers wrote. "Mitochondrial dysfunction was apparent in these monocytes, providing a potential explanation for the increased CV risk associated with T2D."

"Our findings present monocytes as good candidates for predicting cardiovascular complication development among type 2 diabetes patients and highlight the relevance of phenotyping circulating monocytes to assess CV risk in T2D," they concluded.

Reference:

Julla JB, Girard D, Diedisheim M, Saulnier PJ, Tran Vuong B, Blériot C, Carcarino E, De Keizer J, Orliaguet L, Nemazanyy I, Potier C, Khider K, Tonui DC, Ejlalmanesh T, Ballaire R, Mambu Mambueni H, Germain S, Gaborit B, Vidal-Trécan T, Riveline JP, Garchon HJ, Fenaille F, Lemoine S, Carlier A, Castelli F, Potier L, Masson D, Roussel R, Vandiedonck C, Hadjadj S, Alzaid F, Gautier JF, Venteclef N. Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes. Circ Res. 2024 Jan 19;134(2):189-202. doi: 10.1161/CIRCRESAHA.123.322757. Epub 2023 Dec 28. PMID: 38152893.